Immunotherapies, more and more often, are being become in a very effective method against tumors. The patient uses his own immune system to fight them, especially, T-cells are being used. But, what are T-cells, and how do they work?
T-cells, and how do they work:
T cells are a subset of white blood cells, which can specifically recognise and destroy virally infected or cancerous cells,in particular in patients with melanoma, EBV-associated malignancies and nasopharyngeal carcinoma.
The development of an anti-tumor T cell, it is a multiple process. This recognition is done via their T cell receptor, that is designed to interact at the molecular level with proteins on the surface of all cells, in which tumor-associated antigens, expressed by the tumor cells, are processed and presented by professional antigen presenting cells to circulating T cells, which become activated.
Since T cells circulate in the blood, it was imagined that they could be extracted from the blood and transfused into cancer patients, but, for an efficient anti-tumour effect via transfer of immune cells, one needs to select the right cells. A T cell receptor can bind proteins on the surface of other cells with high specificity, and that means, that there is a tiny percent of cells that bear the correct receptor for a given protein.
To solve this problem, researchers have found a way to extract T cells from tumours excised by surgery and then to expand them in vitro in the lab, there the T cells are able to expand to numbers more favourable for making an efficient therapy.
Once returned to the patients, these effector T cells can effectively eradicate tumors that had been resistant to their endogenous precursors, even though both share the same antigenic specificity.
Tumours evolve rapidly and often stop expressing proteins which are targeted by the immune system. Moreover, there could be dramatic consequences if the antigen is expressed in other parts of the body. Many of the antigens expressed by tumor cells are not unique to cancer cells, they are expressed in normal tissues too. Hence, the immune system may have antigen specific T cells that recognize the tumors, but that are rendered unresponsive or tolerant. Because of this, there is an alternative that consists of: adoptively, transfer non-tolerant T cells that have been expanded in vitro in an environment that is capable of breaking their tolerant state and inducing potent effector cells. Scientists have created so called “suicide genes”.
What are “suicide genes”?
They are genes can be added to the T cell at the same time as it is genetically modified to express the tumour-specific receptor. Consequently, it is possible to induce rapid T cell destruction upon treatment, in the event of a dangerous autoimmune response.
Therefore, it was proposed to genetically modify T cells from the blood of cancer patients, to confer a highly specific recognition of cancer proteins. This is feasible, since stable genetic modification of many cell types can be efficiently and safely achieved. It is possible to mutate naturally-occurring T cell receptors to achieve a higher protein-binding ability. For example the chimeric antigen receptor CAR, which can specifically recognize and respond to soluble, immobilized and/or tumor antigens expressed on target cells.
When tumors arise in otherwise normal subjects, the conclusion is that specific T cells were either not induced in vivo, or were unable to destroy the malignant cells.
Recent improvements in molecular biology have increased the applications and effectiveness of this therapeutic approach by allowing the genetic modification of T cells using genes which confer properties such as new antigen specificity or chimeric antigen receptors, beside improve the ability to regulate proliferation of the infused cells.
Since we are born, we are exposed to a great variety of illnesses: from a cold to cancer. For us, a cold it is easy to cure, but cancer, tumors, not at all. That we find several ways to fight against this type of illnesses that are very difficult to treat, is a beginning to start surpassing and finally, achieve cure them. This is going to take us long, but step by step, we can find treatments.
Someday, sadly, one too distant day, this treatments will be available for most of us, but we have to keep researching to achieve the most effective cures and the cheapest ones, for everbody can use them. Everyone deserve to have the opportunity to be cured. Everyone deserve to be healthy. Something very unfair these days.